Studies towards the improvement of an anti-cocaine monoclonal antibody for treatment of acute overdose

https://doi.org/10.1016/j.bmcl.2016.08.081Get rights and content

Abstract

There is currently no clinically-approved antidote for cocaine overdose. Efforts to develop a therapy via passive immunization have resulted in a human monoclonal antibody, GNCgzk, with a high affinity for cocaine (Kd = 0.18 nM). Efforts to improve the production of antibody manifolds based on this antibody are disclosed. The engineering of an HRV 3C protease cleavage site into the GNCgzk IgG has allowed for increased production of a F(ab′)2 with a 20% superior capacity to reduce mortality for cocaine overdose in mice.

Section snippets

Acknowledgements

Funding for this study was provided by the National Institute on Drug Abuse (DA008590 to K.D.J.) and National Institute of Health (TLR1TR001113 to N.T.J.). This is manuscript #29403 from TSRI.

References and notes (17)

  • M.R.A. Carrera et al.

    Pharmacol. Biochem. Behav.

    (2005)
  • J.B. Treweek et al.

    Pharmacol. Biochem. Behav.

    (2011)
  • L.L. Green

    J. Immunol. Methods

    (1999)
  • R. Müller

    Immunochemical Techniques Part E: Monoclonal Antibodies and General Immunoassay Methods

  • Center for Behavioral Health Statistics and Quality

    Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health

    (2015)
  • National Institute on Drug Abuse

    Cocaine

    (2016)
  • European Monitoring Centre for Drugs and Drug Addiction

    European Drug Report 2016: Trends and Developments

    (2016)
There are more references available in the full text version of this article.

Cited by (1)

  • Vaccine design through transition state mimicry of heroin hydrolysis

    2021, Tetrahedron Letters
View full text
© 2016 Elsevier Ltd. All rights reserved.